Morpholine → Methyl 3-methyl-4-morpholin-4-ylbenzoate

HRID 219784Notes

Reaction equation

HRID 219784 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12].C([O-])([O-])=O.[Cs+].[Cs+].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[C:6]([O:8][CH3:9])=[O:7]

Participants

7

Reactant 3

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 3294148Methyl 4-bromo-3-methylbenzoate

Product 1

HCID 67528858Methyl 3-methyl-4-morpholin-4-ylbenzoateYield 84%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of methyl 4-bromo-3-methylbenzoate (5 g, 21.8 mmol) in dry 1,4-dioxane (100 mL), were added dry Cs2CO3 (10.65 g, 32.7 mmol) and morpholine (2.3 g, 26 mmol). The mixture was degassed for 10 min. BINAP (0.67 g, 1.1 mmol) and palladium(II)acetate (0.24 g, 1.1 mmol) were added under N2 and the resulting mixture was refluxed for 15 h. The reaction mixture was filtered through a pad of celite and the filtrate was evaporated. The crude product was purified by flash chromatography, affording the title compound as a yellow solid (4.3 g, 84%). 1H NMR (CDCl3, 400 MHz) δ 7.86-7.90 (m, 2H), 7.13-7.16 (d, 1H), 3.98-4.0 (m, 4H), 3.91 (3H, s), 3.10-312 (m, 4H), 2.45 (3H, s). LC/MS (Method A): 236.0 (M+H)+. HPLC (Method B) Rt 2.24 min (Purity: 95.3%).

Workup

  1. customThe mixture was degassed for 10 min
  2. temperaturethe resulting mixture was refluxed for 15 h
  3. filtrationThe reaction mixture was filtered through a pad of celite
  4. customthe filtrate was evaporated
  5. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-1e594bfb65c4447a9bc2133b32bd3085
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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